Imposing a delay between a behavior and its reinforcer weakens the effectiveness of that reinforcer and decreases its subjective value, a phenomenon referred to as temporal discounting. There is a well-established mathematical model, the hyperbolic discounting function, that describes temporal discounting. Recent research with temporal discounting has made substantial theoretical contributions to our understanding of drug abuse. Imposing a delay between a behavior and a punisher can also diminish the effectiveness of the punisher. The discounting of delayed punishers is particularly relevant to the choice to take a drug of abuse. We often expect negative consequences of drug taking to function as punishers to suppress drug taking. However, these consequences (if they occur at all) are delayed relative to the drug effect, and this delay likely diminishes their effectiveness. Empirical data concerning the actual functional relationship between a delayed punisher and the choice to take a drug of abuse is very limited. Recent research with non-humans has contributed to our understanding of the effects of delayed reinforcement on drug choice. However, no information is available on the effects of delayed punishment on drug taking by non-humans. The overall goal of the present proposal is to examine how imposing a delay between cocaine injections and subsequent punishment alters the ability of that punishment to decrease the likelihood of cocaine self-administration. The proposal has two Specific Aims, each approaching the question from a slightly different perspective. For both Aims we will use a method we developed to study punishment of drug choice by histamine injection. Specific Aim 1 is to examine the relationship between delay of punishment and its effectiveness using a choice between a fixed dose of cocaine followed by different injections of histamine. Our hypotheses are that the effectiveness of punishment of drug choice will be diminished with delay to a histamine injection and that the decrease in effectiveness will be well described by a hyperbolic discounting function. Specific Aim 2 is to examine the relationship between delay of punishment and its effectiveness using a choice between a fixed dose of histamine that follows various doses of cocaine. Our hypotheses are as in Specific Aim 1: the effectiveness of punishment of drug choice will be diminished with delay to a histamine injection and this decrease in effectiveness will be well described by a hyperbolic discounting function. The research in the present proposal will adapt the innovative technique of using an aversive drug infusion to punish self-administration in order to test the hypothesis that the effectiveness of punishment diminishes as a decreasing hyperbolic function of delay to its presentation. An animal model will be particularly useful to push the parametric envelope and begin to establish a conceptual framework within which to understand the control of drug taking by punishment. PUBLIC HEALTH RELEVANCE: We expect negative consequences of drug taking, for example hangover or incarceration, to decrease drug taking. However, negative consequences of drug taking are often delayed in a manner that decreases their effectiveness and may, thereby, contribute to escalating drug abuse. The present project is designed to establish the relationship between the delay to a negative consequence of drug taking and its effectiveness in decreasing the choice to take a drug.